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Biomedical subjects

T Tanabe

Publications and source records attributed to T Tanabe.

At least 199 records · Page 11Linked to original sources
PubMed1997

Retinoids suppress phorbol ester-mediated induction of cyclooxygenase-2.

Cyclooxygenase-2 expression is up-regulated in transformed cells and tumors. Because this enzyme catalyzes the synthesis of prostaglandins, strategies aimed at suppressing its expression may prove useful in preventing or treating cancer. We investigated the ability of retinoids to suppress phorbol ester-mediated induction of cyclooxygenase-2 in human oral epithelial cells. Treatment with phorbol myristate acetate (PMA) resulted in approximately a 3-fold increase in the production of prostaglandin E2 (PGE2). Retinoids [all-trans-retinoic acid (RA), 13-cis-RA, and retinyl acetate] markedly suppressed PMA-mediated increases in amounts of cyclooxygenase-2 (Cox-2) and the production of PGE2. Retinoids also suppressed the induction of Cox-2 mRNA by PMA. Nuclear run-offs revealed increased rates of Cox-2 transcription after treatment with PMA; this effect was inhibited by all-trans-RA. Transient transfection experiments showed that PMA caused about a 2-fold increase in Cox-2 promoter activity, an effect that was suppressed by all-trans-RA. Our data indicate that treatment of oral epithelial cells with PMA is associated with enhanced transcription of Cox-2 and increased production of PGE2. These effects of PMA were inhibited by retinoids.

Anticarcinogenic Agents↗
PubMed1997

Regulation by interleukin-10 and interleukin-4 of cyclooxygenase-2 expression in human neutrophils.

Neutrophils are important effector cells of acute inflammation because of their potential capacity to synthesize various proinflammatory mediators, and inhibition of their production is expected to result in anti-inflammatory effects. In this study, we investigate the effects of the anti-inflammatory cytokines, interleukin-10 (IL-10) and IL-4, on prostanoid synthesis in human neutrophils. Neutrophils isolated from healthy donors constitutively produced a small amount of prostaglandin E2 (PGE2) without any stimulations, whereas they produced a large amount of PGE2 after lipopolysaccharide (LPS) stimulation. IL-10 and IL-4 selectively inhibited their LPS-induced PGE2 production. Inhibition by both cytokines occurred at an early stage of LPS stimulation. Anti-IL-10 treatment of LPS-stimulated neutrophils resulted in enhanced PGE2 production. LPS-induced PGE2 and thromboxane B2 (TXB2) production in aspirin-treated neutrophils was significantly inhibited by IL-10, IL-4, and NS-398. Moreover, IL-10 and IL-4 inhibited LPS-induced cyclooxygenase (COX) activity in neutrophils. Western blot and immunocytochemical analysis showed that COX-2 protein was clearly induced in LPS-stimulated neutrophils and that its induction was inhibited by both IL-10 and IL-4. Moreover, both of these cytokines inhibited COX-2 mRNA expression in LPS-stimulated neutrophils. These results raise the possibility that these two cytokines may both offer potent clinical utility as anti-inflammatory agents in the future.

Cells, Cultured↗
PubMed1997

V beta activation by HIV Nef protein: detection by a simple amplification procedure.

We previously reported that Nef protein from human immunodeficiency virus (HIV) has superantigen properties. However, we were unable to consistently demonstrate V beta-specific expansion by Nef using flow cytometry, possibly due to its lower mitogenic activity compared to prototypic superantigens. Therefore, we developed a simple amplification detection method using immobilized anti-V beta antibodies. Human peripheral blood mononuclear cells from adult donors were treated for 24 h with Nef and restimulated with immobilized anti-V beta antibodies for an additional 72 h. Significant expansion of V beta 5.3 and V beta 18 T-cells were detected in Nef-treated cultures, with expansion of V beta 18 occurring with all donors tested, and V beta 5.3 expansion occurring in 50% of the donors. Variable responses were obtained with V beta 2, V beta 3, and V beta 9. These results were confirmed using the more time-consuming method of reverse transcriptase-polymerase chain reaction (RT-PCR). Thus, this novel, reproducible, and relatively simple method can detect V beta-specific expansion by weak superantigens.

Adult↗
PubMed1997

Cyclic strain is a weak inducer of prostacyclin synthase expression in bovine aortic endothelial cells.

Recent studies indicate that hemodynamic forces such as cyclic strain and shear stress can increase prostacyclin (PGI2) secretion by endothelial cells (EC) but the effect of these forces on prostacyclin synthase (PGIS) gene expression remains unclear and is the focus of this study. Bovine aortic EC were seeded onto type I collagen coated flexible membranes and grown to confluence. The membranes and attached EC were subjected to 10% average strain at 60 cpm (0.5 sec deformation alternating with 0.5 sec relaxation) for up to 5 days. PGIS gene expression was determined by Northern blot analysis and protein level by Western blot analysis. The effect of cyclic strain on the PGIS promoter was determined by the transfection of a 1-kb human PGIS gene promoter construct coupled to a luciferase reporter gene into EC, followed by determination of luciferase activity. PGIS gene expression increased 1.7-fold in EC subjected to cyclic strain for 24 hr. Likewise, EC transfected with a pGL3B-PGIS (-1070/-10) construct showed an approximate 1.3-fold elevation in luciferase activity in EC subjected to cyclic strain for 3, 4, 8, and 12 hr. The weak stimulation of PGIS gene expression by cyclic strain was reflected in an inability to detect alterations in PGIS protein levels in EC subjected to cyclic strain for as long as 5 days. These data suggest that strain-induced stimulation of PGIS gene expression plays only a minor role in the ability of cyclic strain to stimulate PGI2 release in EC. These findings coupled with our earlier demonstration of a requisite addition of exogenous arachidonate in order to observe strain-induced PGI2 release, implicates a mechanism that more likely involves strain-induced stimulation of PGIS activity.

Animals↗
PubMed1997

Experimental replacement of the thoracic inferior vena cava with a high-porosity expanded polytetrafluoroethylene graft wrapped in an omental pedicle flap.

We examined the patency and healing of a high-porosity expanded polytetrafluoroethylene (ePTFE) graft implanted as an interposition graft in the thoracic inferior vena cava (IVC) and wrapped in an omental pedicle flap. High-porosity ePTFE grafts of 60 microns fibril length, with an internal diameter of 10 mm and a length of 4 cm, were implanted in 12 mongrel dogs. In 6 dogs, the grafts were wrapped in omental pedicle flap, and in the remaining 6 the grafts were unwrapped. The animals were killed 4 weeks after the replacement and the grafts were removed for examination. Patency of the graft in both groups was 100%; however, the thrombus-free area in the omentum-wrapped group was significantly larger (P < 0.05) than that in the unwrapped group. Light microscopy revealed the marked infiltration of cells and capillaries within the graft interstices in the omentum-wrapped group. These findings suggest that encapsulation of the high-porosity ePTFE graft is promoted by an omental pedicle flap.

Anastomosis, Surgical↗
PubMed1997

Expanded polytetrafluoroethylene grafts for portal vein replacement: use of omentum wrap to promote graft healing.

This study was designed to reexamine the healing process of expanded polytetrafluoroethylene (EPTFE) grafts with standard porosity (30 microm) and high porosity (60 microm) in portal vein replacement, and to evaluate the effect of an omentum wrap, which has certain functions that promote healing, on graft healing. These grafts, either wrapped by the omentum or not, were placed as portal vein replacements in 24 mongrel dogs. After 1 month, the grafts were retrieved and examined for patency, thrombus-free areas, thickness of the pseudointima, and the total number of cells growing into the graft wall. There were no statistical differences in the patency rates. The high-porosity grafts had a significantly larger thrombus-free area, a thicker pseudointima, and a larger growth of cells than the standard-porosity grafts. The omentum wrap significantly increased the thrombus-free area and stimulated a larger growth of cells in both grafts. The high-porosity grafts plus omentum demonstrated a thrombus-free area of 82.2% vs 27.3% in the standard-porosity grafts. In addition, the migration of fibroblasts and macrophages was most evident in the high-porosity grafts wrapped by the omentum. In conclusion, graft healing enhancement was observed in the high-porosity EPTFE grafts wrapped by the omentum. It is thus suggested that transmural cellular migration plays an important role in the process of graft healing.

Animals↗
PubMed1997

Immunochemical and immunohistochemical study of the 27- and 29-kDa calcium-binding proteins and related proteins in the porcine tooth germ.

Our previous report identified 27- and 29-kDa calcium-binding proteins in porcine immature dental enamel. In this study we revealed that the N-terminal amino acid sequences of the two proteins were identical: LLANPXGXIPNLARGPAGRSRGPPG. The sequence matches a portion of the amino acid sequence of the porcine sheath protein, sheathlin. Porcine tooth germs were investigated immunochemically and immunohistochemically using specific antibodies raised against synthetic peptide that included residues 13-25 of this sequence. The affinity-purified antibodies reacted with several proteins extracted from newly formed immature enamel in immunochemical analyses, especially protein bands migrating at 62, 35-45, 29, and 27 kDa in SDS-polyacrylamide gels. The largest protein detected was a weak band near 70 kDa. In immunochemical analyses of proteins extracted from the inner (old) immature enamel, the antibody reacted faintly with the 27- and 29-kDa proteins. In immunohistochemical preparations, the Golgi apparatus and secretory granules of the secretory ameloblast, and the surface layer of immature enamel showed immunoreactivity. The immunoreactivity of immature enamel just beneath the secretory face of the Tomes' process was intense. No immunoreactivity was found in the Golgi apparatus of the maturation ameloblast. These results suggest that the 70-kDa protein, whose degradation might be very fast, is the parent protein of the 27- and 29-kDa proteins.

Ameloblasts↗
PubMed1997

Intravenously administered macrophage colony-stimulating factor (M-CSF) specifically acts on the spleen, resulting in the increasing and activating spleen macrophages for cytokine production in mice.

IL-6 was transiently expressed in sera of mice after a bolus intravenous injection with LPS and it peaked 2 h later. Intravenous administration of M-CSF at 250 micrograms/kg/day for 5 days prior to an injection of 25 micrograms/kg of LPS elevated the serum IL-6 level 10-fold higher than that of mice which were not given M-CSF. Although M-CSF had no effect on the number of macrophages in alveoli and peritoneal cavity, it tripled the number of spleen macrophages and increased macrophage-progenitor cells 7-fold when injected intravenously. Spleen macrophages from M-CSF-injected mice produced 5-fold more IL-6 in response to LPS-stimulation in-vitro. However, M-CSF-injection had lesser effects on LPS-induced IL-6 production from liver, alveolar and peritoneal macrophages. Exogenously administered M-CSF was detected at higher concentration and for longer duration in the spleen than in any other organs examined. Spleen macrophages incubated in-vitro with more than 1000 U/ml of M-CSF for 3 days also produced more LPS-induced IL-6 than untreated cells. These results indicate that intravenously administered M-CSF not only enhances macrophage development in the spleen, but also primes mature macrophages for cytokine production.

Animals↗
PubMed1997

Macrophage colony-stimulating factor (M-CSF) augments cytokine induction by lipopolysaccharide (LPS)-stimulation and by bacterial infections in mice.

We studied the effects of M-CSF on cytokine induction in vivo by LPS or by bacterial infection by comparing between the serum cytokine levels of mice administered with and without M-CSF. M-CSF at 250 micrograms/kg/day for 3 days significantly augmented serum IL-6 level induced by a subsequent injection of 25 micrograms/kg of LPS. The augmented IL-6-induction was dose-dependent from 50 to 1250 micrograms/kg/day of M-CSF, and required 2- to 3-doses of M-CSF at 250 micrograms/kg/day. Mice primed with M-CSF induced IL-6 in response to a 5-fold lower dose of LPS, and also produced higher levels of IL-1 alpha, IL-10, GM-CSF, TNF-alpha, and IFN-gamma than control mice. The priming effect of M-CSF was transient and reversible, and elicited independently of T-cells. An injection with intact bacteria, such as Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus also induced IL-6 in normal mice, and M-CSF administration augmented the induction of these cytokines. These results showed that M-CSF positively regulates LPS-dependent and -independent cytokine induction, suggesting a defensive effect against infectious agents through enhanced cytokine production.

Animals↗
PubMed1997

An anatomical study of the palmar ligamentous structures of the carpal canal.

To determine which structures should be divided for complete release of the carpal canal, we studied the palmar structures in 12 embalmed and eight fresh cadaveric hands. In all hands, fibres run transversely between the thenar and hypothenar fascia, distal to the flexor retinaculum in a layer separate from it. In fresh cadaveric hands, we first released only the flexor retinaculum as in endoscopic management of carpal tunnel syndrome and then these distal fibres. When the flexor retinaculum was released, the mean distance between the sectioned ends of the flexor retinaculum was 1.3 mm. When the distal fibres were also divided, the mean distance was 6.6 mm. We conclude that release of both the flexor retinaculum and the distal transversely running fibres is essential for complete release of the carpal canal in endoscopic surgery.

Aged↗
PubMed1997

Risk factors for sudden deafness: a case-control study.

In order to investigate risk factors for idiopathic sudden sensorineural hearing loss (sudden deafness), a case-control study was done in 109 patients with sudden deafness who visited our hospital between 1992 and 1994, with 109 controls matched to each patient by gender and age. Odds ratio (OR) and 95% confidence interval (CI) for smoking habits, drinking habits, dietary habits, environmental noise, past history of disease, sleeping hours, appetite, fatigue, incidence of common cold were obtained. Fatigue (OR: 3.28; 95% CI: 1.36-7.90) and loss of appetite (OR: 8:00; 95% CI: 1.00-64.0) elevated the risk for sudden deafness. Those who ate many fresh vegetables were at a decreased risk (OR: 0.48; 95% CI: 0.24-0.96 for light-colored vegetables, OR: 0.55; 95% CI: 0.30-1.02 for green-yellow vegetables). Personal histories of hypertension and thyroid disease, and susceptibility to colds appeared to be positively associated with the risk (0.05 < P < 0.10). Smoking habits, drinking habits and environmental noise had no significant association with sudden deafness. These results suggested that environmental factors, including diet, may be importantly involved in the genesis of sudden deafness.

Adolescent↗
PubMed1997

Investigation of nosocomial infection caused by arbekacin-resistant, methicillin-resistant Staphylococcus aureus.

An outbreak of coagulase VII-producing, arbekacin (ABK)-resistant, methicillin-resistant Staphylococcus aureus (MRSA) occurred between September 1994 and December 1995, involving five different wards. Twenty-one patients developed skin, wound, drainage, or respiratory tract colonization with coagulase VII-producing, (ABK)-resistant MRSA. Phenotypic characteristics (production of enterotoxin and TSST-1, antimicrobial susceptibility) and molecular-typing procedure (plasmid DNA profile, pulsed-field gel electrophoresis [PFGE] and arbitrarily primed polymerase chain reaction [AP-PCR] of chromosomal DNA) in isolated strains were compared. Plasmid analysis identified four different profiles and 19 of 22 strains recovered had identical patterns. PFGE of chromosomal DNA identified three different subtypes and 18 (81.8%) isolates shared the same subtype. AP-PCR also demonstrated that most strains had the same phenotypic characteristics. Although traditional epidemiological methods; for example, coagulase typing, plays a central role in hospital infection control, combination of plasmid DNA profile, AP-PCR, and PFGE may prove to be a particularly informative means of tracking the nosocomial spread of MRSA.

Adult↗
PubMed1997

Structural regions of the cardiac Ca channel alpha subunit involved in Ca-dependent inactivation.

We investigated the molecular basis for Ca-dependent inactivation of the cardiac L-type Ca channel. Transfection of HEK293 cells with the wild-type alpha or its 3' deletion mutant (alpha) produced channels that exhibited prominent Ca-dependent inactivation. To identify structural regions of alpha involved in this process, we analyzed chimeric alpha subunits in which one of the major intracellular domains of alpha was replaced by the corresponding region from the skeletal muscle alpha subunit (which lacks Ca-dependent inactivation). Replacing the NH terminus or the III-IV loop of alpha with its counterpart from alpha had no appreciable effect on Ca channel inactivation. In contrast, replacing the I-II loop of alpha with the corresponding region from alpha dramatically slowed the inactivation of Ba currents while preserving Ca-dependent inactivation. A similar but less pronounced result was obtained with a II-III loop chimera. These results suggest that the I-II and II-III loops of alpha may participate in the mechanism of Ca-dependent inactivation. Replacing the final 80% of the COOH terminus of alpha with the corresponding region from alpha completely eliminated Ca-dependent inactivation without affecting inactivation of Ba currents. Significantly, Ca-dependent inactivation was restored to this chimera by deleting a nonconserved, 211-amino acid segment from the end of the COOH terminus. These results suggest that the distal COOH terminus of alpha can block Ca-dependent inactivation, possibly by interacting with other proteins or other regions of the Ca channel. Our findings suggest that structural determinants of Ca-dependent inactivation are distributed among several major cytoplasmic domains of alpha.

Amino Acid Sequence↗
PubMed1997

Benzo[a]pyrene up-regulates cyclooxygenase-2 gene expression in oral epithelial cells.

Cyclooxygenase may be important in the pathogenesis of smoking-related cancer because it activates carcinogens and catalyzes prostaglandin biosynthesis. We determined the effects of benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon in tobacco smoke, on cyclooxygenase-2 (Cox-2) mRNA, protein and synthesis of prostaglandin E2 (PGE2) in normal and transformed oral epithelial cells. Treatment with B[a]P caused a dose-dependent increase in production of PGE2, with a maximal increase of approximately 100%. Enhanced synthesis of PGE2 was associated with increased amounts of Cox-2 protein. B[a]P also caused a two-fold increase in Cox-2 mRNA in both normal and transformed cells. Transient transfections with a Cox-2 promoter construct showed that B[a]P-mediated induction of Cox-2 mRNA reflected increased transcription. Levels of Cox-1 were unaffected by B[a]P. B[e]P did not affect the synthesis of PGE2 or amounts of Cox-2. These data are important because B[a]P-mediated induction of Cox-2 may predispose to carcinogenesis by enhancing the production of mutagens and the synthesis of prostaglandins.

Benzo(a)pyrene↗
PubMed1997

Difference in affinity for DNA between HMG proteins 1 and 2 determined by surface plasmon resonance measurements.

High mobility group (HMG) proteins 1 and 2 contain two similar but non-identical repeats of DNA-binding domains and an acidic C-terminal. The proposed functions of HMG proteins 1 and 2 imply a probable difference in their DNA-binding abilities. The primary studies by gel retardation assay showed that HMG2 has higher affinity than HMG1 for supercoiled and linear DNA. The DNA-binding of HMG2 appeared strong enough to allow exchange with HMG1 molecule already bound to DNA, while the DNA-binding region of HMG1 showed higher affinity than that of HMG2. In order to compare more quantitatively the affinities, surface plasmon resonance (SPR) measurements using a BIAcore instrument were conducted. The kinetic data indicated that the Kd for the complex of HMG2 with DNA is smaller than that of HMG1, in contrast to the situation for the DNA-binding region of these proteins. The sequence between the second DNA-binding domain and the acidic C-terminal of HMG proteins is required for tight DNA-binding. Also, the acidic C-terminal strongly modulates the DNA-binding ability of each protein. The usefulness of SPR measurement for quantitative analysis of affinity and regions involved in DNA-binding under conditions nearly identical to those in solution is discussed.

Animals↗
PubMed1997

Differences in refractory-period response of canine subendocardium and subepicardium to bunazosin, an alpha1-adrenoceptor antagonist, and propranolol during myocardial ischemia.

Our objective was to investigate the effects of alpha1- or beta-adrenoceptor blockers on endocardial and epicardial refractory-period changes during myocardial ischemia in alpha-chloralose-anesthetized dogs. The first and second diagonal branches of the left anterior descending coronary artery were ligated. The refractory period was determined by an S1-S2 extrastimulus method. Dogs were treated with the alpha1-blocker bunazosin (0.1-0.2 mg/kg, i.v.; n = 16), the beta-blocker propranolol (0.2 mg/kg, i.v.; n = 15), or saline (n = 11). Dogs that developed ventricular tachycardia/fibrillation (VT/VF) during the experiment were excluded from the statistical assessment in refractory periods. In all groups, coronary ligation produced a significant shortening of the refractory period of ischemic epicardial tissue (p < 0.05) but only minimal shortening of ischemic endocardial refractory periods, resulting in an increased difference in repolarization time between the endo- and epicardial sites. Treatment with bunazosin ameliorated this ischemia-related shortening of refractory periods at both the endo- and epicardial sites, with a greater effect seen epicardially (p < 0.05), resulting in values similar to those in the nonischemic tissue. Treatment with propranolol prolonged refractory periods more in the epicardial (p < 0.01) than in endocardial sites, exacerbating the disparity in the refractory period between the endo- and epicardial sites (p < 0.05). Propranolol also prolonged the refractory period of nonischemic tissue (p < 0.05 and p < 0.01 in endo- and epicardial sites, respectively), resulting in a significant difference between the ischemic and normal myocardium at the endocardial site (p < 0.05). Results suggest that the alpha1-blocker bunazosin reduces the refractory-period disparity between the ischemic and normal myocardium without increasing the disparity between the endo- and epicardial surfaces, whereas propranolol produces a greater disparity.

Adrenergic alpha-1 Receptor Antagonists↗